Chronic obstructive pulmonary disease was in 1998 the fourth leading cause of death in the United States (see National Center for Health Statistics Report; 48 (11), (1998)). There has also been an astonishing increase over the last 20 years in asthma and cancer cases among children (see EPA Report 240-R-00-006; December 2000).
Inhalation of therapeutic particles, such as, but not limited to, drug aerosols, is a standard procedure for the treatment of lung airway inflammations and obstructions. This procedure is also now becoming a novel way to combat cancer, diabetes, AIDS, and other diseases, as well as for rapid pain management as inhalation of therapeutics can provide a very effective mechanism of systemic delivery. Existing drug aerosol delivery devices, however, including those that attempt to target specific areas in the lung, exhibit poor efficiencies (e.g., efficiencies ranging from about 5% to about 20%). Consequently, significant portions of the often-aggressive and expensive therapeutic agent used to combat diseases such as cancer, diabetes, and AIDS can deposit on healthy tissue.
For more than 40 years, the most commonly used device for administering therapeutic agents to combat such lung diseases has been the pressurized metered dose inhaler (pMDI). In a pMDI, a propellant (e.g., a non-CFC, such as HFA 134a) ejects, from a pressurized container via a valve, a metered dose of drug in solution (or colloidally suspended) into a spacer where an aerosolized plume is formed and then inhaled. Despite several improvements over the past decades concerning pMDI propellants, actuation mechanisms, and plume modifiers (see Crowder et al., 2001; and Edwards and Dunbar, 2002), pMDI devices suffer from systemic disadvantages (Keller, 1999); for example, the very low target deposition efficiencies, the relatively high aerosol speed, and the requirement for patients to synchronize their breathing inspiration with the actuation of the aerosol device.
Jet and ultrasonic nebulizers have also been used for administering therapeutic agents. These devices deliver therapeutic agents in the form of small droplets or a mist, suitable for single or multiple-dose, deep lung penetration of drugs by breath-actuation. Research efforts thus far have focused on the development of portable, battery-powered jet and ultrasonic aerosol generators. Unfortunately, these devices typically provide unsatisfactory deposition efficiencies.
Use of powder aerosols, either loaded by the user into a dry powder inhaler (DPI) or stored in the device, is another approach for administering therapeutic agents. In passive DPIs, the motion of the inhaled air generates powder particle entrainment and breakup, whereas in active DPIs, stored energy (e.g., blister packs) assists during inhalation in drug powder dispersion (Dunbar et al., 1998). Again, like pMDIs and jet and ultrasonic nebulizers, DPIs typically do not provide adequate targeted deposition efficiencies.
Thus, there is a need in the art for improved aerosol delivery devices, especially aerosol delivery devices that can target specific areas in the lung.